The use of nerve stimulation for treating and controlling a variety of medical, psychiatric, and neurological disorders has seen significant growth over the last several decades, including for treatment of heart conditions. In particular, stimulation of the vagus nerve (the tenth cranial nerve, and part of the parasympathetic nervous system) has been the subject of considerable research. The vagus nerve is composed of somatic and visceral afferents (inward conducting nerve fibers, which convey impulses toward the brain) and efferents (outward conducting nerve fibers, which convey impulses to an effector to regulate activity such as muscle contraction or glandular secretion).
The rate of the heart is restrained in part by parasympathetic stimulation from the right and left vagus nerves. Low vagal nerve activity is considered to be related to various arrhythmias, including tachycardia, ventricular accelerated rhythm, and rapid atrial fibrillation. Stimulation of the vagus nerve has been proposed as a method for treating various heart conditions, including atrial fibrillation and heart failure. By artificially stimulating the vagus nerves, it is possible to slow the heart, allowing the heart to more completely relax and the ventricles to experience increased filling. With larger diastolic volumes, the heart may beat more efficiently because it may expend less energy to overcome the myocardial viscosity and elastic forces of the heart with each beat.
Atrial fibrillation is a condition in which the atria of the heart fail to continuously contract in synchrony with the ventricles of the heart. During fibrillation, the atria undergo rapid and unorganized electrical depolarization, so that no contractile force is produced. The ventricles, which normally receive contraction signals from the atria (through the atrioventricular (AV) node), are inundated with signals, typically resulting in a rapid and irregular ventricular rate. Because of this rapid and irregular rate, the patient suffers from reduced cardiac output, a feeling of palpitations, and/or increased risk of thromboembolic events.
Current therapy for atrial fibrillation includes cardioversion and rate control. Cardioversion is the conversion of the abnormal atrial rhythm into normal sinus rhythm. This conversion is generally achieved pharmacologically or electrically. An atrial defibrillator applies an electrical shock when an episode of arrhythmia is detected. Such a device has not shown widespread clinical applicability because of the pain that is often associated with such electrical shocks. Atrial override pacing (the delivery of rapid atrial pacing to override abnormal atrial rhythms) has not shown sufficient clinical benefit to justify clinical use. Rate control therapy is used to control the ventricular rate, while allowing the atria to continue fibrillation. This is generally achieved by slowing the conduction of signals through the AV node from the atria to the ventricles.
Current treatment techniques have generally not demonstrated long-term efficacy in preventing the recurrence of episodes of atrial fibrillation. Because of the high frequency of recurrences (up to several times each day), and a lack of effective preventive measures, many patients live in a constant state of atrial arrhythmia, which is associated with increased morbidity and mortality.
European Patent Application EP 0 688 577 to Holmström et al., which is incorporated herein by reference, describes a device for supraventricular heart therapy. The device contains an arrhythmia detector for detecting supraventricular arrhythmia and a nerve stimulator for emitting pulses, in response to the detection, to a physiological representative of the parasympathetic nervous system via an electrode system. The electrode system comprises means stimulation means devised to be placeable in an extracardiac position in the neck area of the physiological representative of the parasympathetic nervous system, and for activating this nervous system in direct contact therewith, or via an adjacent blood vessel.
Bilgutay et al., in “Vagal tuning: a new concept in the treatment of supraventricular arrhythmias, angina pectoris, and heart failure,” J. Thoracic Cardiovas. Surg. 56(1):71-82, July, 1968, which is incorporated herein by reference, studied the use of a permanently-implanted device with electrodes to stimulate the right vagus nerve for treatment of supraventricular arrhythmias, angina pectoris, and heart failure. Experiments were conducted to determine amplitudes, frequencies, wave shapes and pulse lengths of the stimulating current to achieve slowing of the heart rate. The authors additionally studied an external device, triggered by the R-wave of the electrocardiogram (ECG) of the subject to provide stimulation only upon an achievement of a certain heart rate. They found that when a pulsatile current with a frequency of ten pulses per second and 0.2 milliseconds pulse duration was applied to the vagus nerve, the heart rate could be decreased to half the resting rate while still preserving sinus rhythm. Low amplitude vagal stimulation was employed to control induced tachycardias and ectopic beats.
U.S. Pat. No. 6,934,583 to Weinberg et al., which is incorporated herein by reference, describes techniques for stimulating the right vagal nerve within a living body via positioning an electrode portion of a lead proximate to the portion of the vagus nerve where the right cardiac branch is located and delivering an electrical signal to an electrode portion adapted to be implanted therein. Stimulation of the right vagus nerve and/or the cardiac branch thereof act to slow the atrial heart rate. Exemplary embodiments include deploying an expandable or self-oriented electrode. Various dedicated and single-pass leads are disclosed, as well as, various electrodes, and stabilization means. The methods include preserving sinus rhythm, avoiding asystole, preserving A-V synchrony, automatically determining parameter combinations that achieve these features, and further (in one embodiment) automatically determining parameter combinations achieve these features and reduce current drain.
Schaldach M, in “New concepts in electrotherapy of the heart,” Electrotherapy of the heart, Springer Verlag Heidelberg, pp. 210-214 (1992), which is incorporated herein by reference, writes that “a general concept of electrical treatment of arrhythmia becomes possible if the neural factors in the arrhythmogenesis are considered. With the powerful tool of monitoring the sympathetic tone by intraventricular impedance measurements, the VIP that was introduced for the restoration of chronotropy will serve as a sensor of the increased neural activity of an impending arrhythmia, therefore making it possible to prevent tachycardia” (p. 210, emphasis in the original).
U.S. Pat. No. 5,318,592 to Schaldach, which is incorporated herein by reference, describes a cardiac therapy system for use with a conventional cardiac pacemaker is controlled by activity signals of the autonomous nervous system (ANS) in a patient's body which constitute a measure for the patient's cardiovascular output requirement. The system includes pickup circuitry for detecting at least the autonomous nervous system activity signals in the patient's body, a control circuit for generating control signals as a function of time and/or intensity of the autonomous nervous system signals picked up in the patient's body, a neurostimulator for changing vascular resistance by nerve stimulation of the patient in adaptation to the patient's intracardial output requirement, in response to control signals from the control circuit, an arrhythmia suppressor for generating anti-arrhythmia stimulation pulses to the patient's heart which are controlled by control signals from the control circuit, and a pump assist for assisting the pumping of the patient's heart in response to control signals from the control circuit.
U.S. Pat. No. 5,203,326 to Collins, which is incorporated herein by reference, describes a pacemaker which detects a cardiac abnormality and responds with electrical stimulation of the heart combined with vagus nerve stimulation. The vagal stimulation frequency is progressively increased in one-minute intervals, and, for the pulse delivery rate selected, the heart rate is described as being slowed to a desired, stable level by increasing the pulse current.
Moreira et al., in “Chronic rapid atrial pacing to maintain atrial fibrillation: Use to permit control of ventricular rate in order to treat tachycardia induced cardiomyopathy,” Pacing Clin Electrophysiol, 12(5):761-775 (May 1989), which is incorporated herein by reference, describe the acute induction of atrial fibrillation with rapid atrial pacing, and an associated reduction in ventricular rate with digitalis therapy. Different treatment protocols are described to induce and maintain atrial fibrillation, in order to bring a patient with NYHA class III-IV congestive heart failure to a more moderate NYHA class II.
Preston et al., in “Permanent rapid atrial pacing to control supraventricular tachycardia,” Pacing Clin Electrophysiol, 2(3):331-334 (May 1979), which is incorporated herein by reference, describe a patient who had continuous supraventricular tachycardia with a ventricular rate of about 170. The arrhythmia was refractory to drugs and DC countershock, and did not convert with atrial pacing. Rapid atrial stimulation (pacing at 300-400/min) controlled the ventricular rate by simulating atrial fibrillation. This therapy was used on a permanent basis for more than five months.
PCT Publication WO 04/110550 to Ben-Ezra et al., which is assigned to the assignee of the present application and is incorporated herein by reference, describes apparatus for treating a subject suffering from spontaneous atrial fibrillation, including an electrode device, adapted to be coupled to a site of the subject selected from the list consisting of: a vagus nerve, an epicardial fat pad, a pulmonary vein, a carotid artery, a carotid sinus, a vena cava vein, and an internal jugular vein, and a control unit, adapted to drive the electrode device to apply an electrical current to the site, and to configure the current to maintain the spontaneous AF for at least about 24 hours, so as to modify blood flow within the atria and reduce risk of thromboembolic events. In other embodiments, the control unit drives an electrode device to apply signals to the vagus nerve, and configures the signals so as to restore NSR, i.e., to induce cardioversion. According to one approach for restoring NSR, the configuration includes repeatedly changing parameters of the stimulation.
The following articles, which are incorporated herein by reference, may be of interest:    Goldberger J J et al., “New technique for vagal nerve stimulation,” J Neurosci Methods 91(1-2):109-14 (1999)    Zhang Y et al., “Optimal ventricular rate slowing during atrial fibrillation by feedback AV nodal-selective vagal stimulation,” Am J Physiol Heart Circ Physiol 282:H1102-H1110 (2002)    Martin P J et al., “Phasic effects of repetitive vagal stimulation on atrial contraction,” Circ. Res. 52(6):657-63 (1983)    Wallick D W et al., “Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs,” Am J Physiol 237(3):H275-81 (1979)    Morady F et al., “Effects of resting vagal tone on accessory atrioventricular connections,” Circulation 81(1):86-90 (1990)    Waninger M S et al., “Electrophysiological control of ventricular rate during atrial fibrillation,” PACE 23:1239-1244 (2000)    Wijffels M C et al., “Atrial fibrillation begets atrial fibrillation,” Circulation 92:1954-1968 (1995)    Goldberger A L et al., “Vagally-mediated atrial fibrillation in dogs: conversion with bretylium tosylate,” Int J Cardiol 13(1):47-55 (1986)    Takei M et al., “Vagal stimulation prior to atrial rapid pacing protects the atrium from electrical remodeling in anesthetized dogs,” Jpn Circ J 65(12):1077-81 (2001)    Friedrichs G S, “Experimental models of atrial fibrillation/flutter,” J Pharmacological and Toxicological Methods 43:117-123 (2000)    Hayashi H et al., “Different effects of class Ic and III antiarrhythmic drugs on vagotonic atrial fibrillation in the canine heart,” Journal of Cardiovascular Pharmacology 31:101-107 (1998)    Morillo C A et al., “Chronic rapid atrial pacing. Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation,” Circulation 91:1588-1595 (1995)    Higgins C B, “Parasympathetic control of the heart,” Pharmacol. Rev. 25:120-155 (1973)    Billette J et al., “Roles of the AV junction in determining the ventricular response to atrial fibrillation,” Can J Physiol Pharamacol 53(4)575-85 (1975)    Garrigue S et al., “Post-ganglionic vagal stimulation of the atrioventricular node reduces ventricular rate during atrial fibrillation,” PACE 21(4), 878 (Part II) (1998)    Kwan H et al., “Cardiovascular adverse drug reactions during initiation of antiarrhythmic therapy for atrial fibrillation,” Can J Hosp Pharm 54:10-14 (2001)
A number of patents describe techniques for treating arrhythmias and/or ischemia by, at least in part, stimulating the vagus nerve. Arrhythmias in which the heart rate is too fast include fibrillation, flutter and tachycardia. Arrhythmia in which the heart rate is too slow is known as bradyarrhythmia.
U.S. Pat. No. 5,700,282 to Zabara, which is incorporated herein by reference, describes techniques for stabilizing the heart rhythm of a patient by detecting arrhythmias and then electronically stimulating the vagus and cardiac sympathetic nerves of the patient. The stimulation of vagus efferents directly causes the heart rate to slow down, while the stimulation of cardiac sympathetic nerve efferents causes the heart rate to quicken.
The following patents, patent application publications, and statutory invention registration, all of which are incorporated herein by reference, may be of interest:    U.S. Pat. No. 5,330,507 to Schwartz    U.S. Pat. Nos. 5,690,681 and 5,916,239 to Geddes et al.    US Patent Publication 2003/0045909 to Gross et al.    U.S. Pat. No. 6,511,500 to Rahme    U.S. Pat. Nos. 5,334,221 to Bardy and 5,356,425 to Bardy et al.    U.S. Pat. No. 5,522,854 to Ideker et al.    U.S. Pat. No. 6,434,424 to Igel et al.    US Patent Application Publication 2002/0120304 to Mest    U.S. Pat. No. 6,564,096 to Mest    U.S. Pat. No. 5,658,318 to Stroetmann et al.    U.S. Pat. No. 6,292,695 to Webster, Jr. et al.    U.S. Pat. RE38,705 to Hill et al.    US Statutory Invention Registration H1,905 to Hill,    U.S. Pat. No. 5,243,980 to Mehra    U.S. Pat. No. 5,170,802 to Mehra    U.S. Pat. No. 5,224,491 to Mehra    U.S. Pat. No. 4,161,952 to Kinney et al.    U.S. Pat. No. 6,134,470 to Hartlaub    U.S. Pat. Nos. 6,073,048 and 6,985,774 to Kieval et al.    U.S. Pat. No. 6,865,416 to Dev et al.    U.S. Pat. No. 6,161,029 to Spreigl et al.    U.S. Pat. No. 5,645,570 to Corbucci    U.S. Pat. No. 7,082,336 to Ransbury et al.
A number of patents and articles describe other methods and devices for stimulating nerves to achieve a desired effect. Often these techniques include a design for an electrode or electrode cuff. The following patents and patent application publications, all of which are incorporated herein by reference, may be of interest:    US Patent Publication 2003/0050677 to Gross et al.    U.S. Pat. No. 4,608,985 to Crish et al.    U.S. Pat. No. 4,649,936 to Ungar et al.    PCT Patent Publication WO 01/10375 to Felsen et al.    U.S. Pat. No. 5,755,750 to Petruska et al.
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